Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
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Yu-Chen Cheng1, Dueng-Yuan Hueng2,3, Hua-Yin Huang1, Jang-Yi Chen4, Ying Chen1,4
1Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan
2Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
3Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan
4Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
Ying Chen, e-mail: [email protected]
Keywords: honokiol, magnolol, autophagy, apoptosis, glioblastoma
Received: November 30, 2015 Accepted: March 28, 2016 Published: April 11, 2016
Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular and animal models. In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. In addition, phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, and Ki67 were decreased after Hono-Mag treatment, showing proliferation inhibition. Hono-Mag treatment also reduced p-p38 and p-JNK but elevated p-ERK expression. Besides, Hono-Mag treatment induced autophagy and intrinsic and extrinsic apoptosis. Both ERK and autophagy inhibitors enhanced Hono-Mag-induced apoptosis in LN229 cells, indicating a rescuer role of ERK. In human GBM orthotopic xenograft model, the Hono-Mag treatment inhibited the tumor progression and induced apoptosis more efficiently than Temozolomide, Hono, or Mag group. In conclusion, the Hono-Mag exerts a synergistic anti-tumor effect by inhibiting cell proliferation and inducing autophagy and apoptosis in human GBM cells. The Hono-Mag may be applied as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment.
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